Paeoniflorin diminishes ConA-induced IL-8 production in primary human hepatic sinusoidal endothelial cells in the involvement of ERK1/2 and Akt phosphorylation

The International Journal of Biochemistry & Cell Biology
Wen-Guang GongGuo-Wu Liang

Abstract

Liver diseases are closely associated with elevated levels of interleukin-8 (IL-8), suggesting the ability to inhibit IL-8 production could enhance the treatment of liver diseases. Paeoniflorin is a major active constituent of dried Paeoniae Radix Alba root (Baishao in Chinese) which is widely used in China to treat liver diseases. We examined the effects and underlying mechanisms of paeoniflorin on IL-8 production in primary human hepatic sinusoidal endothelial cells (HHSECs). Concanavalin A (ConA) at 20 μg/mL produced a 5.2-fold increase in IL-8 mRNA by 8h, and a 14.2-fold rise in IL-8 levels by 16 h. Inhibition of MEK (ERK kinase) and extracellular signal-regulated kinase (ERK) by PD98059 and U0126, or inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked both ConA-induced IL-8 mRNA expression and IL-8 secretion. Paeoniflorin reduced ConA-induced IL-8 mRNA expression and IL-8 release by 57.9% and 52.8%, respectively, and also decreased ConA-stimulated phosphorylation of ERK1/2 and Akt, suggesting paeoniflorin inhibits IL-8 expression and release by inhibiting the ERK1/2 and Akt pathways. Combining paeoniflorin with U0126 or LY294002 at low doses showed supra-additive inhibition of not only phospho-ERK1/2 and...Continue Reading

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Citations

Jul 25, 2017·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Hai JiangYusheng Qiu
Dec 23, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Yu-Feng XingGuang-Dong Tong
May 16, 2020·Frontiers in Pharmacology·Xiao MaYanling Zhao
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Cong WangXuebo Pan
Dec 6, 2018·Revista Española De Enfermedades Digestivas : Organo Oficial De La Sociedad Española De Patología Digestiva·Na LiShiyao Chen
Nov 27, 2020·Food & Nutrition Research·Yonghua ZhangBo Chen
Apr 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yingxia NingXin Luo

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